title: Preliminary results of antiscarring therapy in the prevention of postendoscopic esophageal mucosectomy strictures.
abstract: BACKGROUND
  Esophageal endoscopic submucosal dissection (ESD) is an effective minimally invasive therapy for early esophageal cancer and high-grade Barrett dysplasia. However, esophageal stricture formation after circumferential or large ESD has limited its wide adoption. Mitomycin C (MMC), halofuginone (Hal), and transforming growth factor β3 (TGF-β3) exhibits antiscarring effects that may prevent post-ESD stricture formation.
  
  
  METHODS
  Using endoscopic mucosectomy (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment was excised in a porcine model. The site was either untreated (control, n = 6) or received 40 evenly distributed injections of antiscarring agent immediately and at weeks 1 and 2. High and low doses were used: MMC 5 mg (n = 2), 0.5 mg (n = 2); Hal 5 mg (n = 2), 1.5 mg (n = 2), 0.5 mg (n = 2); TGF-β3 2 μg (n = 2), 0.5 μg (n = 2). The degree of stricture formation was determined by the percentage reduction of the esophageal lumen on weekly fluoroscopic examination. Animals were euthanized when strictures exceeded 80 % or the animals were unable to maintain weight.
  
  
  RESULTS
  The control group had a luminal diameter reduction of 78.2 ± 10.9 % by 2 weeks and were euthanized by week 3. Compared at 2 weeks, the Hal group showed a decrease in mean stricture formation (68.4 % low dose, 57.7 % high dose), while both TGF-β3 dosage groups showed no significant change (65.3 % low dose, 76.2 % high dose). MMC was most effective in stricture prevention (53.6 % low dose, 35 % high dose). Of concern, the esophageal wall treated with high-dose MMC appeared to be necrotic and eventually led to perforation. In contrast, low dose MMC, TGF-β3 and Hal treated areas appeared re-epithelialized and healthy.
  
  
  CONCLUSIONS
  Preliminary data on MMC and Hal demonstrated promise in reducing esophageal stricture formation after EEM. More animal data are needed to perform adequate statistical analysis in order to determine overall efficacy of antiscarring therapy.
authors.affiliation: Department of Surgery, University Hospitals Case Medical Center, 11100 Euclid Ave., Mail Stop LKS 5047, Cleveland, OH, 44106, USA, vwuski@yahoo.com.
authors.forename: Yuhsin
authors.initials: Y
authors.lastname: Wu
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Schomisch
authors.forename: Cassandra
authors.initials: C
authors.lastname: Cipriano
authors.forename: Amitabh
authors.initials: A
authors.lastname: Chak
authors.forename: Richard H
authors.initials: RH
authors.lastname: Lash
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ponsky
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Marks
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D002921:Cicatrix / Q000150:complications / Q000517:prevention & control*; D004195:Disease Models, Animal; D004210:Dissection / Q000009:adverse effects* / Q000379:methods; D004359:Drug Therapy, Combination; D004935:Esophageal Diseases / Q000601:surgery; D004940:Esophageal Stenosis / Q000209:etiology / Q000517:prevention & control*; D004945:Esophagoscopy / Q000009:adverse effects* / Q000379:methods; D005500:Follow-Up Studies; D007267:Injections; D007413:Intestinal Mucosa / Q000473:pathology / Q000601:surgery; D016685:Mitomycin / Q000008:administration & dosage*; D019384:Nucleic Acid Synthesis Inhibitors / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage*; D052999:Quinazolinones / Q000008:administration & dosage*; D013552:Swine; D053782:Transforming Growth Factor beta3 / Q000008:administration & dosage*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D010880:Piperidines; D052999:Quinazolinones; D053782:Transforming Growth Factor beta3; D016685:Mitomycin; C010176:halofuginone